amitriptyline vs fluoxetine
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Side-by-side comparison of amitriptyline and fluoxetine. Data from FDA drug databases (Orange Book, NDC Directory, recalls, shortages) covering 20,000+ approved drugs, plus CMS pricing; see our methodology.
minor Known Drug Interaction
While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).
Elavil
Prozac, Sarafem
Amitriptyline is a medicine used to treat depression. It may take up to 30 days to feel the full effect.
Fluoxetine is a medicine that can help treat depression and other mental health conditions. It belongs to a class of drugs called selective serotonin reuptake inhibitors (SSRIs).
Amitriptyline is used to relieve the symptoms of depression. It works best for a type of depression called endogenous depression. This is depression that comes from within, rather than being caused by outside events.
Fluoxetine can treat major depressive disorder in adults and children. It also treats obsessive-compulsive disorder (OCD) in adults and children. Fluoxetine can help with bulimia nervosa (an eating disorder) and panic disorder. Sometimes, it is used with another medicine called olanzapine to treat depression related to bipolar disorder.
Amitriptyline belongs to a class of drugs called tricyclic antidepressants (TCAs). It works by increasing the levels of certain chemicals in your brain. These chemicals help improve your mood.
Fluoxetine works by increasing the amount of serotonin in your brain. Serotonin is a chemical that helps regulate mood. By increasing serotonin, fluoxetine can help improve mood and reduce symptoms of depression, OCD, and other conditions.
- • Drowsiness
- • Dizziness
- • Weakness
- • Fatigue
- • Headache
- • Abnormal dreams
- • Problems ejaculating
- • Loss of appetite
- • Feeling anxious
- • Feeling weak
- Pain 1,565
- Nausea 1,434
- Headache 1,381
- Fatigue 1,371
- Dyspnoea 1,340
- Drug Interaction 3,335
- Toxicity To Various Agents 3,316
- Nausea 3,233
- Fatigue 3,156
- Completed Suicide 2,904
Antidepressants may increase the risk of suicidal thoughts or actions in children, teens, and young adults. Your doctor should closely monitor you for worsening depression or unusual changes in behavior. Amitriptyline is not approved for use in children.
Antidepressants may increase the risk of suicidal thoughts and behaviors in children, teenagers, and young adults. Watch closely for worsening depression or suicidal thoughts. Tell your doctor right away if you notice any changes in mood or behavior. Fluoxetine is not approved for use in children younger than 7 years old.
Tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. It is not known if amitriptyline will harm your unborn baby. Amitriptyline can pass into breast milk.
Talk to your doctor if you are pregnant or plan to become pregnant. Fluoxetine should only be used during pregnancy if the benefit outweighs the risk to the baby. Breastfeeding is not recommended while taking fluoxetine.
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How to Read This amitriptyline vs fluoxetine Comparison
amitriptyline is classified in the Tricyclic Antidepressant (TCA) drug class, while fluoxetine sits within the Selective Serotonin Reuptake Inhibitor (SSRI) class. Drugs from different classes work through distinct mechanisms, so a head-to-head comparison illustrates trade-offs rather than equivalence. Both drugs are prescription-only, so a licensed provider must authorize use.
Adverse event totals above are pulled from the FDA's Adverse Event Reporting System (FAERS). For these top-ranked reactions alone, amitriptyline has 7,091 submissions while fluoxetine has 15,944. Those figures reflect cumulative reporting volume, not per-patient risk, so older, widely dispensed drugs typically look worse on count alone. These two drugs have a known minor interaction flagged in FDA labeling, attributed to fluoxetine blocks the liver from breaking down amitriptyline and stays in the body for a very long time. this can cause amitriptyline levels to become too high even after you stop taking fluoxetine.. Serious warnings, pregnancy guidance, and contraindications can differ even when indications overlap.
A table cannot represent individual circumstances. Data here is sourced from FDA Structured Product Labels (SPL) and FAERS, both of which update as manufacturers and clinicians submit new information. This registry does not provide medical, treatment, substitution, or medication-change directions for amitriptyline or fluoxetine.
Registry boundary: This comparison displays source-record fields and does not provide individualized medical direction.